Denver Man Gets Gene Therapy to Restore Hearing

Anyone in the know here feel that this drug will still come out in 10 years? Are there any blogs or people on the forums in the trials? How much improvement db wise have they said they have seen and at what khz? I really would love to know if this stuff has shown any success so far according to any participants.

 

I don#t think it will take that long. 2023 is a target date for several military research depts, they are losing soldiers by the truckload from tinnitus.

The detail of the nature of recovery wont be published for a while yet


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"Amanda James first noticed a difference early this year when she picked up a pill bottle at the Norfolk, Va., pharmacy where she worked and shook it next to her right ear.

For the first time, she could hear the pills rattling inside."

KU gene therapy holds new hope for restoring hearing DECEMBER 2, 2015 BY ALAN BAVLEY


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I have not seen anyone on this forum that participated in the GENVEC/Novartis trial.
Only snippets appear in the news and it has been quiet for a few months.
If you want to stay up to date I suggest Stanford: https://hearinglosscure.stanford.edu/
Action on Hearing Loss: http://www.actiononhearingloss.org.uk/
Hearing Health Foundation: http://hearinghealthfoundation.org/
You can subscribe and receive monthly updates.
We al wait with anticipation. But me personally regard 9 years (last year was 10 years) not unrealistic for the simple reason various scientists have been saying this.

But news like this: "For the first time, she could hear the pills rattling inside." I rate very high.
I do not understand that this is not verified with an audiogram. Such important news! Perhaps it has been verified with an audiogram? We don't know. If there has been such a noticeable improvement it means regeneration has take place! How can this be a placebo effect? We can only speculate when there is no more news.

If you read some of the articles you start to realise how big the challenge is, but also that much has been achieved already regarding knowledge.

Discussions on this forum regarding possible future therapies also have been going for a while:

https://www.tinnitustalk.com/thread...ring-loss-using-stem-cells-from-the-uk.13642/

https://www.tinnitustalk.com/thread...in-damage-from-chemotherapy.8137/#post-165248

https://www.tinnitustalk.com/threads/inner-ear-hair-cell-regeneration-—-maybe-we-can-know-more.3131/

Most likely there have been many more discussions regarding regeneration/repair of our hearing.

My hearing loss, hyperacusis and tinnitus have been detrimental to my life. I try to get energy/positivity from following the different news items regarding the science of hearing regeneration.
Accapted it won't happen any time soon, it still gives me energy when I reach rock bottom again.

 

You know what, I think it might be wiser to post what we may know as jpeg in the feed, that way any whistle blowers or inside info does not get indexed in google searches and affect market confidence in the biotech stock. I am aware that when we hype up certain research labs we can affect sentiment. Just saying.

 

I am happy to do this. But do you feel that the hearing restoration field is so small we can influence it?

 

When I speak with anyone in the field I never repeat their names attached to various opinions they may share to others as I don't understand the politics of the peer review system, I would be worried that I could say something stupid that could jeopardize a future collaboration between 2 labs.
Its not the field so much but the market that concerns me, people with lots of money read this stuff to get insight into biotech stock. Investors would consider our opinions as perhaps more genuine than stock briefs from their broker. We know they increased the dosage and there was a problem (it could be minor). These people are not going to just give up on this therapy, they will probably return and repeat the drug at smaller dosages at multiple intervals to see what happens. Once they get an idea of the safe and tolerable limits that wont affect non target tissue, then they can start playing around with different dosages. One big thing here that people are not talking about is improved balance, I cannot believe this as the balance system is far more complex than hearing until i see vemps and hard data that show otherwise but IF it does, it may end up making more money from this side affect than the intended target.

 

Just thinking about this. I do monitor stock movements from different companies in the hearing restoration field.
With the idea, that if something important happens, this influences stock. (It did happen with GENVEC and hopefully will happen again when they continue the trial). Having no experience at all in this area I regard this as a long shot.

 

I am not going to pretend I understand the market well, but for now we must realize they have the financial power to make these trials a reality. The investors of this trial went batshit crazy after the safety pause. Solicitors were cold calling them to get litigation rolling, but Swirsky purchasing the stock before the pause was a master stroke that will keep the lawyers at bay. The trouble is, that these people dont always disclose the full details to investors.

Pharma Secrecy - Brad Loncar - 2015

 

@attheedgeofscience , have you heard anything else from him seeing it's been a year out. Has he had any improvements or any complications?

Also, do you still believe it's realistic to have a hearing loss "cure" by 2025? By cure I mean some therapy that can lead to hearing gains in the ear without a hearing aid or external device, that would lead to 20db or greater improvements across the main khz measured by ents?

 

I wouldnt count on it

 

We discussed his case within the hidden Team Trobalt forum here on TinnitusTalk. I mentioned that someone with Meningitis (as a cause of hearing loss) would not represent a good candidate for a case study such as this. Another member of Team Trobalt, @Zimichael followed up with GenVec about that - an hour long call in fact. It is unclear what happened exactly, but apparently Novartis had some influence over GenVec about their choice of enrollment candidate (i.e. Rob Gerk): they - GenVec - did not want someone with Meningitis enrolling (but Novartis saw it differently).

I believe there have now been several other candidates who have gone through with the procedure. Perhaps the outcome from those have been more convincing (check yourself about that).

Here is the company presentation from an event I already mentioned earlier on in this thread.

GenVec

Depends on your auditory starting point. To my knowledge, GenVec's procedure is aimed towards patients with significant hearing loss. The reason is that re-grown hair cells are not of the same pristine condition as the hair cells we are born with. So hearing threshold starts at 20-25 db (not 0 db). The average person such as yourself probably would not really benefit from the procedure, therefore. As far as I know...

Stem cell research (using embryonic stem cells) may change that. Good luck, however, growing inner ear hair cells in a petri-dish and re-introducing them into the cochlear. Grafting will present a challenge, I am sure.

But then again, why invent something when there is already an existing procedure which works quite well: cold laser therapy.

Lastly, attached are a couple of research papers on MSC procedures (animal studies). I did share one case study from a human in the stem cell thread (should be easy to find).

Stanford research is also worth keeping up-to-date on...

https://hearinglosscure.stanford.edu

 

I agree with you, and I'm doing this therapy with Dr Wilden, but if some cells are dead it's too late ? Laser helps just sick cells ?

And for your stem cell therapy, the fact you improve your T, do you think it was linked to new "hair cells" in your ear thanks to stem cell ? Can we say stem cell therapy are just over control for ears nowadays ? And the guy of Stanford or Great Britain try to control it ?

 

@attheedgeofscience , So, for someone who has hearing loss at 40db 8khz and 30db 4-6khz (and greater at higher khz), you think it could help them out?

I'll try LLLT soon here if I can afford a machine. I can't afford to make a trip out to Europe and there is nowhere nearby me.

Ultimately, I just want my hearing back to above 20-25db for anything >=8kz.

I just am losing hope though really.

 

Hair cell regeneration (Outer/Inner hair cells) plus spiral ganglion neurons need to form for hopefully the best opportunity at restoring ones ability to be able to distinguish a small set of frequencies from the others depending on which location of hair cells in the cochlea are able to be regenerated or even developed as new hair cells. Both sides need to work together for an overall well working ear to brain process to ensue.

I'm telling you though, don't waste $20,000 or whatever is needed to pay for what ATEOS went through. He did a good deed of testing that sort of therapy out, although it hasn't been FDA approved, but I'm sorry it's not going to allow you to hear better. There's more to our hearing than just a magical "repair" from Cord Blood Stem Cells. Maybe I'm talking out of my behind, but unless there's significant proof in that Cord Blood Stem Cell Clinical Trial being done on infants with hearing loss/issues then it's not going to give you the results you're looking for and can be looked at more as a placebo.

 

Then what is a realistic timeframe on SOME therapy regenerating hair cells consistently? I never planned to go do the therapy in Thailand or China as i cant afford it anyhow (much less probably wont be alive for long either).

If the answer is idk or it depends, then I'm of the sad belief its not coming out in my meaningful lifetime. Meaning its time for me to jump in front of a train.

 

Like I said, these stem cells therapies may benefit greatly for other medical issues but theoretically there is no way those therapies, even if they state they can treat hearing loss, will give you the results you are looking for. You still have maybe a decade before a real hearing loss stem cell treatment could be allowed for human use. You never know though with a lot these countries thriving in the stem cell race, it could come sooner or it could take way longer. You just gotta stay up to date on science. Maybe contribute to it a little if you can to help speed up the process.

Were you the one who posted on here about blasting music on headphones in your ears and then developing ringing and how you want to end your life because you already have physical medical issues and you don't see how things could get any better?

Have you gotten any hearing tests done?

P.S.
I've heard some news about hair cell regenerating treatments that are being worked on and hopefully will go into clinical trials in the next couple years. There is hope. You just gotta take everything day by day.

P.S. again, if you are the person who posted on here about the headphone usage then I've got some more news for you.

 

Yes, I got hearing test done (an ENT didn't give me prednisone at that time either after hearing test, which was about 4 weeks out at that point. The saw me 2 weeks earlier too). I am at 40db at 8khz, 30db at 6khz, and 30db at 4 khz. Other ear is fine. I know I had a massive drop in the one ear, that is where the T came from.

Can I ask you what good news you heard? What is the things that will be coming to trial in next couple of years? Also what other news do you have?

Seriously, if in 10 years they will have a realistic cure for getting my hearing loss up to at least 20db, then I would be happy and may stick around then. If it's going to be longer than that, then I'm sorry but its not worth sticking around for me. And I really don't want to hear that it's going to happen if it's realistically not going to happen.

 

It's just hard to believe that headphones caused damage to specific hair cells in your cochlea. Do you still have ringing from the incidents? The headphones as explained in studies by MD's will most likely destroy the nerve fibers that allow one to hear frequencies that each hair cell picks up. Although noise will damage hair cells, you would of had to of played music at full volume for a good amount of hours straight to realistically damage your hair cells like that.

It's funny because I listened to music a lot over the past decade, I played in a band for 5 years without protecting my hearing at all. I had many hearing tests performed over the past year. All have shown no signs of significant wear on my hair cells. Specific tests for the hair cells showed that they were functioning properly. But my processing abilities and hearing with other noises going on is terrible now. I can't even listen to music anymore.

I still just don't believe that headphones have destroyed functional properties of your inner or outer hair cells. How loud and long were you listening to them?

 

The doctor assumed it was that, but chances are it could have just been SNHL that coincidentally occurred around the same time. Either way, doctors were idiots and didn't give me correct treatment. So, whatever caused it I didn't get correct treatment for it. So guess I'm screwed. Unless you have some hope to offer?

 

I've been thinking about this a bit since this thread popped back up. To bring this back to gene therapy - which is the topic of this thread - rather than stem cells, we can look at the Norvantis/Genvec trial. The gene being manipulated is ATOH1. The first paper demonstrating ATOH1 could improve hearing in (mature) deaf mammals was published in February 2005 (http://www.nature.com/nm/journal/v11/n3/full/nm1193.html). The entry in clinicaltrials.gov for the Norvantis trial was May 2014 (https://clinicaltrials.gov/ct2/show/NCT02132130?term=cgf166&rank=1), and the first recipient was in October (I think) 2014. If the trial had not been paused, they were looking for a completion date of August 2017 - and they could still hit that if it truly is a pause that ends soon. So that is almost 12 1/2 years from publication of the animal results through Phase I/II trials in humans or looked at another way just under 10 years from paper to the start of a Phase I trial. On top of that, at this point we also don't know how well it has worked.

There are a number of things to keep in mind with this:
1) There's been a lot of work since 2005 so presumably there are some potential trials in the works. (In other words, regardless of how this trial comes out, it seems very unlikely that we have to wait another 10 years for another trial.)
2) It's always possible that, as scientists learn more, the time from animal trials to human trials will decrease.
3) On the down side, ATEOS is right that the initial treatments will be for severe or profound hearing loss in adults. Presumably children who are born deaf due to a genetic issue will also be high on the list.

 

Jdjd09, I know how you feel. I have profound hearing loss in the right ear and severe hearing loss in my left ear. Without my hearing aid in the left ear, I have about 10% hearing. I an 27 and have been deaf/hard of hearing since I was 2. That is more than 25 years! In 25 years, there still has not been an therapy released or anything close to it. I, like, Nick Pyzik believe the an solid "cure" is light years away. From my own research and talking to researchers deeply involved in the hearing restoration world; it is at least 25-50 years away. Why? Because they are still discovering new genes in the inner ear. You asked about ATOH1; by introducing one specific gene will not do much. The good thing which has came out from genvec's trial is that it shows the inner ear is reachable. Here is a quote from my conversation with a very famous researcher:

"As you know, there are concerns about the safety of stem cell based treatments and I fear that beside safety concerns, we need to see substantial improvements in efficacy of regenerative strategies in animal experiments before any of the current experimental “treatments” can be applied to humans. This is pretty much the state of research for stem cell transplantation, gene therapy, and drug treatments. My expectations are however that we will see novel experimental drug trials in patients in the next 5 years. This said, I would consider these drugs (Atoh1 gene therapy included) as “version 1” of treatments that will have plenty of room for improvements. I doubt that these will be good enough to replace cochlear implants, but I hope that version 1 will become v2 and then v3 and so on and that at some point in the future, biological treatments will replace cochlear implants"

I believe a cocktail of genes bundled up together and then injected in the inner ear will be beneficial than a single gene being used.

I second the above quote from the researcher. In my opinion, I would be happy to see an fully internal cochlear implant with better speech perception and speech understanding releases. A cochlear implant which is close to "natural" hearing, one which sounds less robotic and allows one to block unnecessary background noise. One which is totally in the head; that would cool.

 

I think your are correct about the "coctail of genes" that will be needed to fully restore hearing however I believe your time frame of 25-50 years is a bit off. They have discovered a few more other than ATOH1 since then. I think that in about 10 years we will see trials for treatments where they are activating a combination of genes. This is at least what I have read in articles about the subject.

The thing with stem cell therapy as well as gene therapies is that once they become safe and mainstream it won't take long until they are being used for pretty much any condition out there.

Also as a molecular biologist I have studied developmental biology (of course) and I don't think we will ever see solutions with transplanting grafts and so on. A surgical approach is just not going to ever work because we are dealing with such delicate tissues. It would be as mad as going to the butcher for a knee surgery.

The solution for many ailments in the future will be making our own bodies do the work. Our bodies have been able to make it right once and all of that information is still in there in every one of our cells (except erythrocytes of course). It's just a matter of figuring out how to jump start the process again. And that will most certainly require turning on and off a coctail of genes.

 

I understand people having differing thoughts on when there will be a "cure". The sad fact is, we just do not know. Research is all good, but there are many barriers even to conduct clinical trials which itself can take many years; as we have seen with Genvec's trial. The following is from Stanford Initiative to Cure Hearing loss:

"We are discovering that almost all of these causes of hearing loss, whether from noise exposure, chemicals, or aging, have significant genetic components. A few hundred genes are thought to be involved in hearing loss, but to date only half of them have been identified. At SICHL, our research is dedicated to characterizing this missing knowledge by discovering these genes".

 

Yes of course but one should not forget the escalation in medical and technical advancements. We have learned more in the last 5 years than we have in the previous 5 and even more than in the 5 years before that. The more we know the faster the rate of new progress becomes. To discover the first gene responsible for the development of hearing is the hardest one because you have to develop new techniques and so on. After you've done something a few times it becomes routine and a sort of rense and repeat.

It took years to sequence the first gene. Once that was done it didn't take long before we had sequenced the whole genome. So I believe that the coming 5 years will be even more productive than the last 5. Just look at our whole society. It took us about 150 000 years to develop the first combustion engine and then in the 100 years after that we put a man on the moon. Things in development are simply moving faster now than they used to.

 

Yes, of course. Future generations will be always have the opportunity. We just need to be realistic; inner ear research is one of the most pain stalking out there. The inner ear area itself is enclaved in bone.

I, for one who has lived with deafness all my life have always hoped something will come out. It has been an barrier to dreams, relationships and friendships. If something comes when I am old, I wouldn't take it. I rather pass the opportunity to someone younger. My time would have passed and I rather live with full hearing in my prime when I needed it the most.

Like you said, advancements are alwsys good. I hope the same

 

Well, the difference is I wouldn't pass up an opportunity to get rid of this horrible affliction if given the chance. I don't believe you would be taking any one's place. If a solution for us comes out at some point everyone will eventually get their chance.

 

The ear has immune privilege, also it has a closed loop to other parts of the body, it is a fortress against pathogens, it is theorized that virus loaded cells actually access the ear through the mouth, then from the brain cisterns radiate upwards to the facial nerve and hop across to nerve viii, not from the outer ear or pinna as most people perceive. A way to deliver a payload will have to be direct to the inner ear, thats why stem cells introduced into the arm intravenously probably would have no effect on the ear.

 

They will definitely complete the task of curing deafness, when es derived otic progenitors are trialled they will be able to regenerate not just one but ALL cell types of the ear. The power of the stem cell is mind-boggling, but can we control it, the risks will be great.

 

Why do I feel that medical science has not been developing at the same speed technology has.
I could be wrong, but that is what it looks like to me. We hear almost every day in the news about revolutions in technology.

But we still need hearing aids and tinnitus masking sound generators. And hyperacusis??? Just try to get used to the discomfort. Modern day hearing aids are probably very high technology. Despite this, the principle of dealing with hearing loss is still similar to one of putting an old fashioned funnel in your ears. Like our an casters used to do 100 years ago. I know a hearing aid will not give me better hearing For the simple reason that my hearing starts to distort at already moderate levels. Complex sounds like in peoples voices are difficult to make sense of. Also with my "good" ear.
Something @Nick Pyzik also has been talking about.

I will not forget my visit to my ENT. "Yep, you got damaged hearing. No nothing can be done. Get used to it. Why are you so stressed? Tinnitus is not life threatening. I won't kill you."
Not the tinnitus, surely, but the impact of tinnitus and hyperacusis on a person is a different discussion. When every morning you wake up and think "@#$$ another day". Go to sleep in the evening and think "good, another day past". You start to think about the comment: "tinnitus and hyperacusis is not life threatening".

It still is common when you develop tinnitus after a noise trauma an ENT will tell you "No hearing damage. visible in your audiogram." Excellent news for insurers. They will gladly follow the ENTs finding and discard the tinnitus, harder of hearing and hyperacusis complaints of the claimant.
Despite this "perfect" audiogram people have more difficulty understanding other people in a noisy environment.
Just very recently scientists start to understand that much more is damaged in the cochlea than is visible on a audiogram.
But the majority of tests are still conducted on a rudimentary level. Again: good for insurance claims.

Yesterday was a very tire sum tinnitus and hyperacusis day. Today starts like a repeat of yesterday. I am angry.

 

This is because medical improvments take a lot of testing, checking and then retesting and rechecking. If you want to make a new microprocessor your new idea is out on the market in less then a year if you want it to. You don't have to do all the trials and so on.

Medical advancement is actually advancing it's just that today we get the "new" stuff that was really invented 10 years ago. And since we might have read about it a decade ago it feels old.

Medical science has had some major advancements. Of course it hasn't been equally in all fields and some are harder to make breakthroughs than others. I made this example in another thread about my best buddy that had a prematurely born child. 10 years ago the survival rate for children born in the same week as his daughter was less than 10%. Today it's above 90%!

What we are dealing with here is probably one of the hardest conditions to treat of all. There is no easy way to test a drug and you can't even have a decisive test to confirm if the patient even has it! If we compare it to, let's say cancer. It's right there! We can acctually see it in a scan! There is no way of seeing tinnitus.

Also there are no terminal patients that have a month to live that you can enroll in experimental procedures. And to top it all of you are dealing with the brain. The one organ we don't fully understand and that is more complex than anything we know of. If we were to build a computer that is as complex as the brain it would be the size of a city and consume the power output of a nuclear power plant. That's why we haven't had that breakthrough yet! But we will! We will...